This is an application to test the feasibility of reducing tinnitus by pairing left vagus nerve stimulation (VNS) with tone presentations to reorganize the auditory cortical frequency map. Approximately ten percent of adults experience some degree of tinnitus, the perception of sound in the absence of an environmental acoustic stimulus. For one percent of the adult population, the experience is so severe that it makes it difficult to hear, work, or sleep. There is no general treatment for tinnitus, although several treatments can alleviate or reduce tinnitus in some patients. Recent studies suggest that pathological reorganization of frequency mapping in the auditory cortex is a major contributor to the symptoms of tinnitus in many patients. In normal individuals, there is an evenly distributed tonotopic organization of the cortical auditory map and spontaneous synchronous activity is not observed. When tinnitus is present, the tonotopic organization is unevenly distributed and spontaneous synchronous activity is observed, which is believed to account for the tinnitus. This spontaneous activity is believed to result from the uneven tonotopic organization of the auditory cortex. We propose to develop a neuroprosthetic approach for the treatment of tinnitus by pairing tone presentations with stimulation of the VNS to induce therapeutic reorganization of the uneven tonotopic quality of the auditory cortical frequency map. Electrophysiological studies will be used to evaluate the effect of tone pairing with VNS to direct frequency specific changes on both tonotopic mapping and spontaneous synchronous activity. Behavioral studies conducted in an animal model of tinnitus will evaluate the potential clinical efficacy of this proposed therapy. Based on preliminary observations, pairing tones with VNS is expected to 1) realign the auditory cortex frequency map, 2) decrease spontaneous synchronous activity in the auditory cortex, and 3) eliminate the tinnitus perception. Combining this technique with current pharmacological, behavioral, and auditory therapies could greatly improve outcomes for a currently unmet medical need. PUBLIC HEALTH RELEVANCE: MicroTransponder, Inc. is developing a novel treatment for tinnitus. This is an application to test the feasibility of reducing tinnitus by pairing left vagus nerve stimulation (VNS) with tone presentations to reorganize the auditory cortical frequency map. Current pharmacological, auditory, and training therapies are likely to be more effective if coupled with a mechanism to stimulate therapeutic cortical plasticity.